Personalizing Radiotherapy for Endometrial Cancer: Balancing Innovation and Quality of Life

In this interview, Kara D. Romano, MD, University of Virginia, discusses advancements in radiation therapy for endometrial cancer, the integration of systemic therapies, the impact of treatment on quality of life, and the role of clinical pathways in optimizing care.

Please introduce yourself by stating your name, title, and any relevant clinical experience you’d like to share?

Kara D. Romano, MD: My name is Kara Romano, MD. I am associate professor in the Department of Radiation Oncology at the University of Virginia with clinical and research expertise in gynecologic cancers and brachytherapy.

What advancements in radiation therapy delivery are most promising for improving outcomes in endometrial cancer?

Dr Romano: Advanced radiotherapy techniques, such as intensity modulated radiotherapy (IMRT), stereotactic body radiotherapy (SBRT), and image guidance, have increased our ability to target the tumor or areas at risk for tumor spread while minimizing toxicity. In addition, technologies such as MRI-guided radiotherapy (MRgRT) further improve our ability to safely treat tumors to curative doses and reduce the dose, and thus toxicity, to surrounding normal organs. MRI-guided radiotherapy is utilized in both brachytherapy and external beam therapy. Future applications of imaging and technology for delivering safe and effective radiotherapy will continue to develop.

How do you see the integration of systemic therapies with radiation evolving for endometrial cancer treatment?

Dr Romano: This is a great question. The optimal treatment of endometrial cancer in the era of molecular risk stratification is an open and ongoing area of investigation. We know that the molecular profile of endometrial cancer is both prognostic and predictive of recurrence patterns and survival by subgroup. Some patient subgroups may benefit from treatment de-escalation, while others benefit from treatment escalation, including immunotherapy (IO) and trastuzumab.

Radiotherapy (RT) has historically played a key role in the adjuvant treatment of patients with endometrial cancer by reducing the risk of locoregional recurrence. Systemic therapy, on the other hand, plays a complementary role in reducing the risk of distant recurrence. As systemic therapy, including traditional chemotherapy, IO, and targeted therapies, evolves, the traditional role of RT will need to be reexamined in each molecular subset.

RT has known immunomodulatory effects, including immune stimulation and immune suppression, depending on the environment—an important consideration with the administration of IO. In addition, pelvic RT has been demonstrated to be safely delivered concurrently with IO in the definitive treatment of cervical cancer. However, future successful combinations of radiation with systemic therapy will need to consider the timing, sequencing, volume, and dose/fractionation of RT in a potentially new model.

We will continue to evaluate creative ways to incorporate RT in the treatment of endometrial cancer. As systemic therapy continues to improve, “salvage RT” with curative intent delivered at the time of recurrence becomes more valuable. Focal RT with SBRT and brachytherapy will play a key role, and perhaps the timing of RT needs to be reconsidered to maximize the immune response.

What are the key quality-of-life issues faced by patients undergoing radiation therapy for endometrial cancer?

Dr Romano: Every cancer treatment has toxicity to consider, and the toxicity profile of RT varies significantly between vaginal brachytherapy and pelvic external beam RT.

Vaginal brachytherapy is generally very well tolerated, with mild acute toxicity and primary late toxicity of vaginal stenosis, which can impact sexual function. Vaginal stenosis can potentially be minimized with lower dose/fractionation schedules and the use of vaginal dilators. For some patients, sexual function is an important quality-of-life consideration, and in others it is not a priority. This is an individual patient discussion, and open trials are currently evaluating the impact of varying brachytherapy schedules on toxicity.

Thanks to advancements in technology for external beam therapy, such as IMRT, we have significantly improved patient-reported outcomes of toxicity in recent years. Key toxicities of pelvic RT include bowel and bladder side effects both in the acute and late setting, as well as vaginal stenosis. Anecdotally and prospective randomized data, toxicity with pelvic RT is less than with systemic therapy, which may be important quality-of-life consideration for some patients when determining the optimal treatment.

Focal RT, including SBRT and MRI-guided treatments, has less acute toxicity due to the limited treatment volume, but also has potential for more serious late toxicity. Advancing technology will continue improve these outcomes, and thoughtful consideration of when to use these RT tools is important.

How can clinical pathways incorporate newer radiation techniques to standardize and improve patient care for those with endometrial cancer?

Dr Romano: This is also a great question. As technology improves and the role of RT with systemic therapy evolves, I think it is valuable to consider focal and shorter course treatments. This may include hypofractionation (short-course RT) to the pelvis or IMRT/SBRT delivered directly to the tumor without including the draining lymphatics. Thoughtful research that continues to evaluate the questions of RT sequencing, volume, and dose/fractionation will help optimize the benefits of RT (eg, locoregional control) and combination therapy (eg, stimulating an immune response) while minimizing toxicity.